In complex diseases such as cancer, drug combinations have the potential to provide durable treatment responses, minimize adverse events, and limit development of resistance (U.S. Department of Health and Human Services Food and Drug Administration, “Guidance for Industry. Codevelopment of Two or More New Investigational Drugs for Use in Combination,” (June 2013)). A related approach to combination therapy is single agent polypharmacological drugs such as multi-targeted kinase inhibitors. However, a lack of systematic design approaches and a historical reliance on serendipity has limited the number of new polypharmacological drugs (Anighoro et al., “Polypharmacology: Challenges and Opportunities in Drug Discovery,” J. Med. Chem. 57:7874-7887 (2014); Reddy et al., “Polypharmacology: Drug Discovery for the Future,” Expert Rev. Clin. Pharmacol. 6:41-47 (2013)). An intentional, rational approach to polypharmacology, especially in the context of the whole animal, would significantly expand the ability to develop complex therapeutics. Further, achieving “balanced polypharmacology” in the context of the whole animal can reduce overall toxicity by balancing a drug's effects on cellular and tissue networks.
The present invention is directed to overcoming these and other deficiencies in the art.